Prognostic significance of c-kit mutation in localized gastrointestinal stromal tumors.

PURPOSE: Constitutive mutational activation of c-kit has been found to be associated with the pathogenesis of gastrointestinal stromal tumors (GISTs). The prognostic significance of c-kit mutations, however, is still controversial. EXPERIMENTAL DESIGN: We examined 86 patients curatively resected for localized GIST. Genomic DNA was extracted from paraffin-embedded tumor tissues. Exons 9, 11, 13, and 17 of the c-kit gene were amplified by PCR and sequenced. RESULTS: Mutations in exon 11 were detected in 61 tumors, and mutations in exon 9 were observed in three tumors, whereas no mutations were detected in exons 13 or 17. The overall c-kit mutation frequency was 74%. Amino acid alterations in the 61 tumors with exon 11 mutations were deletion in 33 tumors, substitution in 20, both deletion and substitution in 4, insertion in 1, and duplication in 3. Histologically, tumors with c-kit mutations showed higher mitotic counts and higher cellularity. The 5-year relapse-free survival (RFS) in patients having GISTs with c-kit mutations was 21%, compared with 60% in those without c-kit mutations. Significantly higher RFS rates were observed in patients with tumors having mitotic counts < 5 mitoses/50 high power field, spindle-cell histology, tumor size < 5 cm, or gastric GISTs. Multivariate analyses indicated association of poorer RFS with a higher mitotic count > or = 5 of 50 high power fields; odds ratio (OR) = 3.0], presence of c-kit mutations (OR = 5.6), and a larger tumor size (> or = 5 cm; OR = 4.2). CONCLUSIONS: The presence of c-kit mutation, along with high mitotic count and larger tumor size, was an independent factor for poor prognosis in patients with localized GISTs.     

The impact of simulated distal interphalangeal joint fusion on grip strength

This study assessed the impact of distal interphalangeal (DIP) joint fusion on grip strength and how this may be related to a profundus quadriga. Nineteen adults (12 men and 7 women) with an average age of 32.6 years (range: 24-61 years) underwent a series of grip strength measurements with simulation of DIP arthrodesis to the index, long, and index and long (index-long) fingers. The nondominant hand served as a control for the testing. All participants were tested in the same manner: baseline dominant and nondominant hands without DIP block followed by blocking of DIP flexion on the dominant hand only for index, index-long, and long finger alone. Nondominant hands also were tested each time, but without blocking to serve as a control for normal changes in grip strength with repeated testing. Grip strength values were compared to baseline for each trial using the Student's t test. Significant decreases in grip strength were seen for all DIP blocking compared with baseline, but no significant differences were noted in the equivalent trial in the nondominant, nonblocked hand. These findings may have clinical relevance when performing DIP arthrodesis.     

FLT3-TKD mutation in childhood acute myeloid leukemia.

Mutations of receptor tyrosine kinases are implicated in the constitutive activation and development of human hematologic malignancies. An internal tandem duplication (ITD) of the juxtamembrane domain-coding sequence of the FLT3 gene (FLT3-ITD) is found in 20-25% of adult acute myeloid leukemia (AML) and at a lower frequency in childhood AML. FLT3-ITD is associated with leukocytosis and a poor prognosis, especially in patients with normal karyotype. Recently, there have been three reports on point mutations at codon 835 of the FLT3 gene (D835 mutations) in adult AML. These mutations are located in the activation loop of the second tyrosine kinase domain (TKD) of FLT3 (FLT3-TKD). The clinical and prognostic relevance of the TKD mutations is less clear. To the best of our knowledge, there has been no report to describe FLT3-TKD mutations in childhood AML. In this pediatric series, FLT3-TKD mutations occurred in three of 91 patients (3.3%), an incidence significantly lower than that of FLT3-ITD (14 of 91 patients, 15.4%) in the same cohort of patients. None of them had both FLT3-TKD and FLT3-ITD mutations. Sequence analysis showed one each of D835 Y, D835 V, and D835 H. Of the three patients carrying FLT3-TKD, two had AML-M3 with one each of L- and V-type PML-RARalpha, and another one had AML-M2 with AML1-ETO. None of our patients with FLT3-TKD had leukocytosis at diagnosis. At bone marrow relapse, one of the four patients examined acquired FLT3-ITD mutation and none gained FLT3-TKD mutation.     

Thallium-201 single-photon emission computed tomography as an early predictor of outcome in recurrent glioma.

PURPOSE: With limited response rates and potential toxicity of chemotherapeutic treatment in patients with recurrent glioma, reliable response assessment is essential. Currently, the assessment of treatment response in glioma patients is based on the combination of radiologic and clinical findings. However, response monitoring with computed tomography (CT) or magnetic resonance imaging (MRI) is hampered by several pitfalls and is prone to interobserver variability. The aim of this study was to establish the value of thallium-201 single-photon emission computed tomography (201Tl-SPECT) as a predictor of overall survival and response to chemotherapy in recurrent glioma, and to compare the value of 201Tl-SPECT with that of CT and MRI. PATIENTS AND METHODS: We studied patients who underwent CT or MRI and 201Tl-SPECT before chemotherapy (n = 57), and patients who also had undergone CT or MRI and 201Tl-SPECT after two courses of chemotherapy (n = 44). The value of the radiologic variables (CT-MRI tumor size, 201Tl-SPECT tumor size, and maximal tumor intensity) at baseline and at follow-up in predicting overall survival, and the percentage of patients alive and progression-free at 6 months (APF6) were examined using Cox regression and logistic regression analysis. RESULTS: Both at baseline and at follow-up, 201Tl-SPECT maximal tumor intensity was the strongest predictive variable and was inversely related to overall survival and APF6. In particular, progression of maximal tumor intensity after two courses of chemotherapy was a powerful predictor of poor outcome. CONCLUSION: 201Tl-SPECT is superior to conventional CT-MRI in the early prediction of overall survival and response to chemotherapy in patients with recurrent glioma.     

Carotid endarterectomy using the eversion technique

Carotid endarterectomy by the eversion technique allows for all of the benefits of conventional endarterectomy but obviates the need for a distal suture line on the smaller internal carotid artery, and thus batching. Carotid artery reanastomosis onto the bifurcation can be quickly and simply performed with almost no risk of closure-related restenosis, given the anastomosis is on the larger of 2 arteries. In our experience of over 3,000 eversion carotid artery endarterectomies, the restenosis rate has been less than 1% judged by rigorous duplex follow-up. In this article, the technique and utility of eversion carotid endarterectomy is discussed.     

~(89)Sr治疗骨转移癌疼痛研究

 目的　评价放射性核素89锶 (89Sr)对骨转移癌的止痛疗效和不良反应 ,并探讨其在癌性骨痛治疗中的应用范围。方法　观察 35例骨转移癌患者使用89Sr治疗后的止痛疗效、肿瘤标记物水平的变化、不良反应及血液学毒副反应。结果　89Sr止痛总有效率为 71 .4 % ,其中来源于前列腺癌和乳腺癌的骨转移癌患者有效率达到 80 .0 %。少数肿瘤标记物水平有下降。副反应主要为轻度可逆性的骨髓造血功能损害。89Sr对血生化无明显不良影响。结论　89Sr是治疗骨转移癌疼痛的一种安全有效的方法